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theses

Osteoarthritis (OA), the principal source of physical disability and impaired quality of life in the US, is a chronic age-related disease characterized by the progressive destruction of articular cartilage, leading to total joint deterioration. OA severely burdens the US healthcare system with overall cost of ~185 billion dollars a year. Recent evidence suggests that inflammatory cytokine and chemokine release signals and cellular infiltration ultimately lead to matrix degradation and cartilage destruction. There is currently no cure for OA. Existing treatments alleviate symptoms initially; however, they are not able to alter disease progression and disease development eventually proceeds. Therefore, there is a need to develop effective therapies that could alter OA progression and promote healing in osteoarthritic joints.

One approach to alter the progression of OA has been intra-articular administration of mesenchymal stromal cells (MSC) which secrete anti-inflammatory and regenerative factors that could alter the underlying pathophysiology of OA. However, these cells are not long-lasting when freely administered. We have previously demonstrated that alginate encapsulation of MSC lengthens their survival and promotes their secretory function, a characteristic that could serve as long term treatment for OA. In this dissertation, we investigated whether treatment with MSC or alginate-encapsulated MSC can provide sustained reduction of OA mediated joint inflammation and destruction, and promote healing in an in vitro model of OA.

In addition, we aimed to improve on current OA in vitro models which often rely on chemically or mechanically stimulated chondrocytes, the sole cell component of articular cartilage, without taking into consideration other cell types and their interactions in the articular joint. We developed a multi-culture stackable insert system that allows for the 3D co-culture and investigation of multiple cell types, cell-cell interactions, and cell responses to their environment. Such experiments could provide powerful new tools and therapies in an otherwise irreversible progressive disease.

ETD_10560

Ph.D.

Includes bibliographical references

doi:10.7282/t3-6k2d-gc05

ETD doctoral

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